In January 1790 he returned to Montpellier, was elected a member of the municipality, co-founded the Jacobin Club in that city, and on the flight to Varennes of King Louis XVI in 1791, he drew up a petition to invite the National Constituent Assembly to proclaim a Republic —the first in date of such petitions.

On 9 February 1792, he succeeded in having a law passed confiscating the possessions of the émigrés, and tried to arrange the deportation of non-juring priests to French Guiana.

In the year after he denounced Jean-Paul Marat's placards as inciting to murder, summoned Georges Danton to give an account of his ministry, supervised the furnishing of military supplies to the French Revolutionary Army, and was a strong opponent of Charles François Dumouriez, in spite of the general's great popularity.

Cambon incurred the hatred of the theist Maximilien Robespierre (see Cult of the Supreme Being) by proposing the suppression of the pay to the clergy, which would have meant the separation of church and state.

Although he took part in toppling Robespierre in July 1794, Cambon was targeted and pursued by the Thermidorian Reaction, and had to live in hiding in Montpellier.